Structural Changes and Functional Control of the Tick-Borne Encephalitis Virus Glycoprotein E by the Heterodimeric Association with Protein prM

Virology ◽  
1994 ◽  
Vol 198 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Franz X. Heinz ◽  
Karin Stiasny ◽  
Gudrun Püschner-Auer ◽  
Heidemarie Holzmann ◽  
Steven L. Allison ◽  
...  
Keyword(s):  
Structural Changes ◽  
Encephalitis Virus ◽  
Glycoprotein E ◽  
Virus Glycoprotein ◽  
Tick Borne Encephalitis ◽  
Functional Control ◽  
Tick Borne Encephalitis Virus

scholarly journals Computational and Rational Design of Single-Chain Antibody against Tick-Borne Encephalitis Virus for Modifying Its Specificity

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1494
Author(s):  
Ivan K. Baykov ◽  
Pavel Y. Desyukevich ◽  
Ekaterina E. Mikhaylova ◽  
Olga M. Kurchenko ◽  
Nina V. Tikunova
Keyword(s):  
Rational Design ◽  
Fold Increase ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Glycoprotein E ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

Tick-borne encephalitis virus (TBEV) causes 5−7 thousand cases of human meningitis and encephalitis annually. The neutralizing and protective antibody ch14D5 is a potential therapeutic agent. This antibody exhibits a high affinity for binding with the D3 domain of the glycoprotein E of the Far Eastern subtype of the virus, but a lower affinity for the D3 domains of the Siberian and European subtypes. In this study, a 2.2-fold increase in the affinity of single-chain antibody sc14D5 to D3 proteins of the Siberian and European subtypes of the virus was achieved using rational design and computational modeling. This improvement can be further enhanced in the case of the bivalent binding of the full-length chimeric antibody containing the identified mutation.

scholarly journals Adaptation of Tick-Borne Encephalitis Virus to BHK-21 Cells Results in the Formation of Multiple Heparan Sulfate Binding Sites in the Envelope Protein and Attenuation In Vivo

2001 ◽  
Vol 75 (12) ◽  
pp. 5627-5637 ◽  
Author(s):  
Christian W. Mandl ◽  
Helga Kroschewski ◽  
Steven L. Allison ◽  
Regina Kofler ◽  
Heidemarie Holzmann ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Encephalitis Virus ◽  
Surface Glycoprotein ◽  
Glycoprotein E ◽  
Recombinant Viruses ◽  
Adult Mice ◽  
Tick Borne Encephalitis ◽  
Significant Attenuation ◽  
Tick Borne Encephalitis Virus

ABSTRACT Propagation of the flavivirus tick-borne encephalitis virus in BHK-21 cells selected for mutations within the large surface glycoprotein E that increased the net positive charge of the protein. In the course of 16 independent experiments, 12 different protein E mutation patterns were identified. These were located in all three of the structural domains and distributed over almost the entire upper and lateral surface of protein E. The mutations resulted in the formation of local patches of predominantly positive surface charge. Recombinant viruses carrying some of these mutations in a defined genetic backbone showed heparan sulfate (HS)-dependent phenotypes, resulting in an increased specific infectivity and binding affinity for BHK-21 cells, small plaque formation in porcine kidney cells, and significant attenuation of neuroinvasiveness in adult mice. Our results corroborate the notion that the selection of attenuated HS binding mutants is a common and frequent phenomenon during the propagation of viruses in cell culture and suggest a major role for HS dependence in flavivirus attenuation. Recognition of this principle may be of practical value for designing attenuated flavivirus strains in the future.

scholarly journals Structural insights into tick-borne encephalitis virus neutralization and animal protection by a therapeutic antibody

2021 ◽  
Author(s):  
Ivan K. Baykov ◽  
Grzegorz Chojnowski ◽  
Petr Pachl ◽  
Andrey L. Matveev ◽  
Nina A. Moor ◽  
...  
Keyword(s):  
Rational Design ◽  
Encephalitis Virus ◽  
Glycoprotein E ◽  
Animal Protection ◽  
X Ray Crystallography ◽  
Tick Borne Encephalitis ◽  
Late Endosomes ◽  
Lateral Ridge ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) causes about 5-6 thousand cases annually, while there is still no effective treatment for this virus. To fill this gap, a high-affinity chimeric anti-TBEV antibody ch14D5 has previously been constructed, and high protective activity in a murine TBEV model has been shown for this antibody. However, the mechanism of action of this antibody and the recognized epitope have not been known yet. In this study, it is shown by X-ray crystallography that this antibody recognizes a unique epitope on the lateral ridge of the D3 domain of glycoprotein E, which is readily accessible for binding. The orientation of this antibody relative to the virion surface makes bivalent binding possible, which facilitates the cross-linking of glycoprotein E molecules and thus blocking of surface rearrangements required for infection. Since the antibody tightly binds to this protein even at pH ~ 5.0, it locks the virion in an acidic environment inside the late endosomes or phagosomes and, therefore, effectively blocks the fusion of the viral and endosomal/phagosomal membranes. We believe that this is why the ch14D5 antibody does not induce an antibody-dependent enhancement of infection in vivo, which is critical in the development of antibody-based therapeutic agents. In addition, the structure of the antibody-glycoprotein E interface can be used for the rational design of this antibody for enhancing its properties.

scholarly journals ANALYSIS OF DOMAIN SPECIFICITY OF THE PROTECTIVE CHIMERIC ANTIBODY ch14D5a AGAINST GLYCOPROTEIN E OF TICK-BORNE ENCEPHALITIS VIRUS

2018 ◽  
Vol 22 (4) ◽  
pp. 459-467 ◽  
Author(s):  
I. K. Baykov ◽  
L. A. Emelyanova ◽  
L. M. Sokolova ◽  
E. M. Karelina ◽  
A. L. Matveev ◽  
...  
Keyword(s):  
Expression System ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Fab Fragment ◽  
Surface Plasmon Resonance Analysis ◽  
Glycoprotein E ◽  
Resonance Analysis ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
System 1

A drug for the prevention and therapy of tick-borne encephalitis virus is being developed on the basis of the protective chimeric antibody ch14D5a. At the same time, the epitope recognized by this antibody on the surface of glycoprotein E has not been localized yet. The aim of this work was to identify the domain of glycoprotein E, to which the protective antibody ch14D5a binds. As a result, four recombinant variants of glycoprotein E were generated using the bacterial expression system: (1) the rE protein containing the domains D1, D2, and D3 of glycoprotein E; (2) the rED1+2 protein containing domains D1 and D2; (3) the rED3_301 protein, which is domain D3 of glycoprotein E, and (4) the rED3_294 protein comprising domain D3 and a hinge region connecting domains D1 and D3. The rED3_294 and rED3_301 proteins were obtained in soluble monomeric form. The rE and rED1+2 proteins were extracted from the inclusion bodies of Escherichia coli. Using Western blot analysis and surface plasmon resonance analysis, it was demonstrated that the protective chimeric antibody ch14D5a and its Fab fragment bound specifically to domain D3 of glycoprotein E. Since the antibodies recognizing epitopes on the surface of domain D3 do not tend to cause antibody-dependent enhancement of the infection as compared to antibodies directed to domains D1 and D2, the data obtained confirm the promise of using the antibody ch14D5a in the development of a therapeutic preparation against the tick-borne encephalitis virus.

scholarly journals The effect of differences in the third domain of the glycoprotein E of tick-borne encephalitis virus of the Far Eastern, Siberian and European subtypes on the binding of recombinant D3 proteins with a chimeric antibody

2019 ◽  
Vol 23 (3) ◽  
pp. 256-261
Author(s):  
I. K. Baykov ◽  
A. L. Matveev ◽  
L. A. Emelianova ◽  
G. B. Kaverina ◽  
S. E. Tkachev ◽  
...  
Keyword(s):  
Amino Acid ◽  
Spatial Arrangement ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Therapeutic Drug ◽  
Glycoprotein E ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

Currently, a therapeutic drug based on recombinant antibodies for the prevention and treatment of tick-borne encephalitis virus (TBEV) is developed in ICBFM SB RAS, and the chimeric antibody ch14D5 is considered as one of the key components of this drug. It was previously shown that this antibody is directed to the domain D3 of the glycoprotein E of TBEV. It was previously shown that this antibody is able to protect mice from the European subtype of TBEV, strain “Absettarov”, and the presence of virus-neutralizing activity against the Far Eastern subtype of TBEV, strain 205 was also shown for this antibody. However, it remains unclear whether this antibody exhibits selectivity for different subtypes of TBEV. The aim of this study was to investigate the effect of amino acid sequence differences of recombinant D3 domains derived from the glycoprotein E of TBEV of the Far Eastern, Siberian and European subtypes on the binding of the protective antibody ch14D5 to these proteins. Using Western blot analysis and surface plasmon resonance, it was shown that ch14D5 antibody has the highest affinity (KD= 1.7±0.5 nM) for the D3 domain of the TBEV of the “Sofjin-Ru” strain belonging to the Far Eastern subtype of the virus. At the same time, the affinity of ch14D5 antibody for similar D3 proteins derived from “Zausaev”, “1528-99” and “Absettarov” strains of the Siberian and European subtypes of TBEV was noticeably lower (KD= 25±4, 300±50, 250±50 nM, respectively). In addition, information about the spatial arrangement of amino acid residues that are different for the studied recombinant proteins indicates that the epitope recognized by the ch14D5 antibody is in close proximity to the lateral ridge of D3 domain of E glycoprotein.

TBE in South Korea

2019 ◽  
Author(s):  
Joon Young Song
Keyword(s):  
South Korea ◽  
Human Case ◽  
Encephalitis Virus ◽  
Surveillance Studies ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Although no human case of tick-borne encephalitis (TBE) has been documented in South Korea to date, surveillance studies have been conducted to evaluate the prevalence of tick-borne encephalitis virus (TBEV) in wild ticks.

TBE in Slovakia

2019 ◽  
Author(s):  
Jana Kerlik
Keyword(s):  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

The former Czechoslovak Republic was one of the first countries in Europe where the tick-borne encephalitis virus (TBEV) was identified.

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